MANAGEMENT OF DRUG-INTERACTIONS WITH CYCLOSPORINE

Major advances in transplantation and in the treatment of autoimmune disorders have been achieved with the use of cyclosporine (CsA). During the past 10 years a variety of drug interactions have been reported to occur with CsA. These may be classified as either pharmacokinetic or pharmacodynamic in origin. Pharmacokinetic interactions are manifested by either an increase or decrease in the CsA concentration. The predominant mechanism of interaction is alteration in the cytochrome P-450 metabolism of CsA, however, some of the drugs may also affect its absorption, distribution, and elimination. Pharmacodynamic interactions include enhanced nephrotoxicity. Management of these events mandates proactive measures such as assessing the interactive potential of each new agent, measuring CsA concentrations more frequently when either initiating or discontinuing other agents, adjusting the dosage of CsA as necessary, and monitoring patients' clinical status to ensure efficacy and minimize the risk of toxicity.